Metyrapone Study for Patients Diagnosed With Mild Autonomous Cortisol Secretion - MACS

Официальное название

A Phase II, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Metyrapone in Subjects Diagnosed With Mild Autonomous Cortisol Secretion (MACS)

Обзор

single-center, randomized, double-blind, placebo-controlled Phase 2 study to evaluate safety and efficacy of overnight metyrapone in patients with MACS.

Подробное описание

This study is a double blind, placebo-controlled phase II trial of the safety and efficacy of Metyrapone, in the treatment of MACS. Subjects will be remotely screened and interested qualified subjects will be remotely consented. Subjects will be randomized 2:1 for 6 months of the main study. At 6 months, two options will be available for subjects for months 6-12: open-label arm, observational arm.

Вмешательства

• Препарат Metyrapone 250 mg Oral Tablets
  Subjects will receive metyrapone beginning at 500 mg and titrating up to 1000 mg
• Препарат Placebo
  Subjects will receive placebo at 500 mg dose and titrated up to 1000 mg to match interventional arm and prevent unblinding

Первичные конечные точки

• Glucocorticoid to androgen ratio [Срок оценки: 3 and 6 months]
• Delta salivary cortisone [Срок оценки: 3 and 6 months]

Вторичные конечные точки (7)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Срок оценки: 0-6 months]
• Change in body mass index (BMI) [Срок оценки: 3 and 6 months]
• Adrenal insufficiency symptoms as assessed by the AddiQoL Survey [Срок оценки: Baseline, 1 week post dose titration, 3 and 6 months]
• Adrenal insufficiency as assessed through morning ACTH and cortisol measurements. [Срок оценки: baseline, 3, 6 months]
• Improvement in hyperglycemia [Срок оценки: 3 and 6 months]
• Improvement in hypertension [Срок оценки: 3 and 6 months]
• Quality of life as assessed by SF36 form [Срок оценки: 3 and 6 months]

Критерии участия

Критерии включения

• Provide written informed consent.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Age ≥ 18 years
• Diagnosed with MACS i. at least 2 abnormal post-dexamethasone cortisol results1 mg post-dexamethasone cortisol >1.8 mcg/dL or ii. 8 mg post-dexamethasone cortisol >1 mcg/dL b. Historical dexamethasone suppression test results can be used if performed within 24 months prior to enrollment.
• Adrenal imaging phenotype consistent with benign disease (adrenal adenoma/s, macronodular or micronodular adrenal hyperplasia)
• At least one of the following comorbidities:

• obesity (BMI>30 kg/m2)
• dysglycemia
• dyslipidemia
• hypertension
• osteopenia
• osteoporosis
• fragility fractures
• Ability to take oral medication and be willing to adhere to the study intervention regimen.
• For persons of childbearing potential: : agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤ 5% per year during the treatment period and for 1 month after the last dose of study treatment.
• Stable timing for bedtime for at least one week prior to on-site study visits.
• History of difficulty providing blood via standard blood draw methods

Критерии исключения

• Planned alternative therapy for MACS within 12 months after joining the study.
• Current use of oral exogenous glucocorticoid therapy
• Current use of opioid therapy >20 MME/day
• Planned use of oral exogenous glucocorticoid therapy
• Planned use of opioid therapy >20 MME/day
• Use of injectable glucocorticoid within 6 weeks prior to Day 1
• Investigator's judgement based on history/physical examination that a comorbidity or concomitant medication may impact the hypothalamic-pituitary-adrenal axis or steroid metabolome
• Uncontrolled intercurrent illness including, but not limited to:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements
• Pregnancy or lactation
• Known allergic reactions to metyrapone
• Suspected false positive post-dexamethasone cortisol results due to increased metabolism, poor absorption, or noncompliance with dexamethasone
• Treatment with another investigational drug or other intervention within lower than specific therapy washout period

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07138274 · 25-007821

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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